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Discovery of CRISPR/Cas Mechanisms and Genome Editing Potential Wins Nobel Prize in Chemistry 2020

The Nobel Prize in Chemistry this year recognized the work of two scientists across the Atlantic. Dr. Jennifer Doudna at the University of California, Berkeley, and Dr. Emmanuelle Charpentier at Umeå University in Umeå, Sweden, had the honor to share the Nobel prize for elucidating the mechanisms behind the CRISPR/Cas9 system in bacterial immunity and their innovative proposal and work adapting this system for precise genome editing. Their discoveries have led to the worldwide adaptation of CRISPR as the standard for genetic engineering of cells and animal models.

  • Jennifer A. Doudna, Ph.D., is a Professor of Molecular and Cell Biology and Chemistry at the University of California, Berkeley. She is also a Howard Hughes Medical Institute (HHMI) Principal Investigator since 1997.

What is the CRISPR/Cas System?

The CRISPR/Cas system evolved in bacteria as an adaptive immune mechanism, which confers protection against invading bacteriophages and plasmids. This immune defense system relies on the activities of two main molecule types; (1) a Cas nuclease, which cleaves double-stranded DNA (dsDNA), and (2) a guide RNA (gRNA), which targets specific viral DNA sequences.

CRISPR/Cas9 Complex: The guide RNA consists of two RNA molecules, the CRISPR RNA (crRNA) and the transactivating RNA (tracrRNA), which act together to target a specific genome sequence and interact with the Cas9 nuclease. A linker loop, a modification introduced to connect the two RNA molecules, facilitates the implementation of gene editing strategies (Jinek et al. 2012). The CRISPR/Cas9 complex recognizes a protospacer adjacent motif (PAM), found downstream of the targeted genomic sequence. CRISPR Handbook

Celebrating the Nobel Prize Recipients

“This year Nobel Prize in Chemistry to Doudna and Charpentier reflects the huge impact CRISPR/Cas technology has had in biomedical research and the huge potential it holds to tackle big challenges in human health, agriculture or climate change, just to name a few. It is also a celebration of women in STEM getting the recognition they deserve. Jennifer and Emmanuel are now recognized, wonderful role models for young women. I personally know Jennifer Doudna very well, from being her colleague at Berkeley and her collaborator and friend. She is a power house, brilliant, poised, extremely hard working, and generous. I cannot think of anyone more deserving of this recognition. We are not surprised, but we are all delighted for her here at Berkeley!”

Dr. Eva Nogales is interested in understanding the molecular mechanism underlying essential cellular functions. She uses electron microcopy and image analysis to obtain atomic models of molecular machines involved in the regulation of gene expression and the internal organization of the cell. She has collaborated with Prof. Doudna to determine the structure of several CRISPR complexes.

"It is a great pleasure to congratulate the winners of the 2020 Chemistry Nobel Prize, Jennifer Doudna and Emmanuelle Charpentier. RNA guided endonucleases have already revolutionized biomedical research and have the potential to transform medicine."

Dr. Niren Murthy is a professor in the Department of Bioengineering at the University of California at Berkeley. Dr. Murthy’s scientific career has been focused on the molecular design and synthesis of new materials for drug delivery and molecular imaging. The Murthy laboratory has been recently focused on developing non-viral delivery vehicles that can deliver Cas9 protein, gRNA and Donor DNA in vivo, and has collaborated with the Doudna laboratory to develop new Cas9 delivery vehicles.

How the CRISPR/Cas9 System Works for Genome Editing?

Specific binding of the CRISPR/Cas9 complex to its target DNA sequence is directed by a guide RNA and constrained by the presence of a PAM sequence downstream of the targeted DNA. Once binding occurs, Cas9 nuclease domains independently cut the unwound DNA strands resulting in a blunt-ended double strand break (DSB). Following DNA cleavage, the cellular machinery targets the site for DNA repair through two main mechanisms: Non-Homologous End Joining (NHEJ) and Homology-Directed Repair (HDR). The outcome for DNA repair through these two mechanisms is distinct, with NHEJ leading to short random insertions or deletions (indels), and HDR resulting in precise repairs. For genome editing, depending on the desired modification, guide RNAs may be designed to knock-out specific genes, or by additionally supplying a specific DNA template, to knock-in a specific sequence of interest (Rosenblun et al. 2020).

The State of Current CRISPR/Cas Based Applications

When it comes to CRISPR technology innovation seems endless. The number of novel applications for CRISPR/Cas editing tools continues to grow. This is partly driven by the growing number of startups aiming to harness this powerful approach to tackle a variety of issues from human disease to sustainable agriculture, among others.

Several startups are focused on applying CRISPR editing technology in the area of gene and cell therapy. For example, Beam Therapeutics is using CRISPR base editors to modify, ex vivo, blood and immune cells for downstream therapeutic applications. Additionally, companies such as Sherlock Biosciences and Mammoth Biosciences are leveraging the unique property of Cas nucleases to degrade non-targeted DNA or RNA through collateral cleavage to develop rapid diagnostic tests with simple readouts for point of care diagnostics. In the agriculture sector, PLANTeDIT is a startup based in Ireland using CRISPR/Cas9 editing tools to produce “DNA-free” sustainable plant products, a strategy which aims to bypass “GMO” related customer-distaste as well as regulatory issues.


Deltcheva, E. et al. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature (2011) doi:10.1038/nature09886.

Jinek, M.et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science (80-. ). (2012) doi:10.1126/science.1225829.

Makarova, K. S. et al. Evolution and classification of the CRISPR-Cas systems. Nature Reviews Microbiology (2011) doi:10.1038/nrmicro2577.

Rosenblum, D., Gutkin, A., Dammes, N. & Peer, D. Progress and challenges towards CRISPR/Cas clinical translation. Advanced Drug Delivery Reviews (2020) doi:10.1016/j.addr.2020.07.004.

Wiedenheft, B. et al. RNA-guided complex from a bacterial immune system enhances target recognition through seed sequence interactions. Proc. Natl. Acad. Sci. U. S. A. (2011) doi:10.1073/pnas.1102716108.

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